Mesenchymal Stem Cells Carrying Viral Fusogenic Protein p14 to Treat Solid Tumors by Inducing Cell–Cell Fusion and Immune Activation by Yao Wang, Xunlei Pang, Ruirui Li, Jiuzhou Chen, Chen Wen, Huihuang Zhu, Tingyu Long, Jianjie Li, Lijun Zheng, Youcai Deng, Junnian Zheng, Bo Xu

“…Background: Chimeric antigen receptor (CAR)-based immune cell therapies attack neighboring cancer cells after receptor recognition but are unable to directly affect distant tumor cells. …”
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Clinically relevant orthotopic pancreatic cancer models for adoptive T cell transfer therapy by Gregory B. Lesinski, Chrystal M. Paulos, Maggie Phillips, Jacklyn Hammons, Isaac Karpovsky, Zaid Mahdi, Natalie K. Horvat, Megan M. Wyatt, Margaret A. Hall, Cameron J. Herting, Richard A. Moffitt

“…Interestingly, we found that chimeric antigen receptor (CAR) T cells redirected to recognize mesothelin on these tumors that signal via CD3ζ and 41BB (Meso-41BBζ-CAR T cells) infiltrated the tumors of mice bearing stroma-devoid KPC-Luc orthotopic tumors, but not MT-5 tumors.Conclusions Our data establish for the first time a reproducible and realistic clinical system useful for modeling stroma-rich and stroma-devoid PDAC tumors. …”
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Outcomes of Idecabtagene Vicleucel Therapy in Patients with Relapsed/Refractory Multiple Myeloma: A Single-Institution Experience by Aaron Trando, Farid Ghamsari, Philip Yeung, Caitlin Costello, Ila Saunders, Ah-Reum Jeong

“…<b>Background/Objectives:</b> Idecabtagene vicleucel (ide-cel), an anti-B-cell maturation chimeric antigen receptor T-cell therapy, represents an unprecedented treatment option for relapsed/refractory multiple myeloma (R/R MM). …”
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Targeting sphingosine 1-phosphate receptor 3 inhibits T-cell exhaustion and regulates recruitment of proinflammatory macrophages to improve antitumor efficacy of CAR-T cells agains... by Weiting Liao, Ge Gao, Xia He, Pei Shu, Qizhi Ma, Benxia Zhang, Diyuan Qin, Yongsheng Wang

“…Backgrounds Chimeric antigen receptor (CAR)-modified T cells (CAR-T) are limited in solid tumors due to the hostile tumor microenvironment (TME). …”
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Construction and characterization of chimeric FcγR T cells for universal T cell therapy by Juanjuan Zhao, Manling Chen, Xudong Li, Zhaoqi Chen, Wei Li, Rongqun Guo, Min Wang, Zhongxing Jiang, Yongping Song, Jianxiang Wang, Delong Liu

“…Abstract Background Several approaches are being explored for engineering off-the-shelf chimeric antigen receptor (CAR) T cells. In this study, we engineered chimeric Fcγ receptor (FcγR) T cells and tested their potential as a versatile platform for universal T cell therapy. …”
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Novel banana lectin CAR-T cells to target pancreatic tumors and tumor-associated stroma by Malcolm K Brenner, Challice Bonifant, Norihiro Watanabe, Mary K McKenna, Daniel Brenner, Ada Ozcan, Maureen Legendre, Dafydd G Thomas, Christopher Ashwood, Richard D Cummings, David M Markovitz

“…We address both limitations with a novel class of chimeric antigen receptors based on plant lectins, which recognize the aberrant sugar residues that are a ‘hallmark’ of both malignant and associated stromal cells. …”
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Chimeric cytokine receptor TGF-β RⅡ/IL-21R improves CAR-NK cell function by reversing the immunosuppressive tumor microenvironment of gastric cancer by Yaojun Ren, Min Xue, Xinhui Hui, Xiuyu Liu, Muhammad Asad Farooq, Yiran Chen, Yuzhou Ji, Yixin Duan, Iqra Ajmal, Jie Yao, Wenzheng Jiang

“…Natural killer (NK) cells play a crucial role in the body’s anti-cancer defense, and chimeric antigen receptor (CAR)–NK cell therapy is gaining attention as a cutting-edge and promising treatment method. …”
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Single-chain variable fragment affinity tuning can optimize anti-AML CAR-NK cell functionality by Marianna Zahurak, Ravi Varadhan, Ilias Christodoulou, Ruyan Rahnama, Jun Choe, Huilin Yang, Monika Kizerwetter, Christian Guaraca, Natalie Jordan Holl, Stamatia C Vorri, Megan Zinsky, Danielle G Jones, Nikol Garcia Espinoza, Yun-Huai Kuo, Jamie B. Spangler, Challice L. Bonifant

“…Background Natural Killer (NK) cells have intrinsic anticancer activity that can be redirected toward acute myeloid leukemia (AML) with chimeric antigen receptor (CAR) engineering. Here, we study the functional consequences of CAR binding affinity and targeted epitope on CAR-NK cell activation, cytolytic synapse formation, and antitumor activity.Methods We characterized NK-92 and primary NK cell populations expressing variant affinity AML-specific CARs containing single-chain variable fragments (scFvs, 26292 or 7G3) targeting two epitopes on CD123. 26292 affinity variants were discovered through directed evolution of an error-prone mutagenic library, while 7G3 affinity variants were previously reported. …”
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Genetic disruption of Blimp-1 drastically augments the antitumor efficacy of BCMA-targeting CAR T cells by Anthony M. Battram, Joan Mañé-Pujol, David F. Moreno, Aina Oliver-Caldés, Judit Carpio, Oriol Cardus, Luis Gerardo Rodríguez-Lobato, Álvaro Urbano-Ispizua, Carlos Fernández de Larrea

“…Abstract: Chimeric antigen receptor (CAR) T cells directed against B-cell maturation antigen (BCMA) are an effective treatment for multiple myeloma (MM), but short persistence and frequent relapses are challenges for this immunotherapy. …”
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B7-H3 CAR-T cell therapy combined with irradiation is effective in targeting bulk and radiation-resistant chordoma cancer cells by Kun Wang, Gianpietro Dotti, Soldano Ferrone, Yufeng Wang, Yin P Hung, Tao Ma, Giulia Cattaneo, Xinhui Wang, David O Osei-Hwedieh, Tara A Walhart, Joseph H Schwab

“…This study explores the efficacy of B7-H3 chimeric antigen receptor T (CAR-T) therapy in vitro and in vivo.Methods Chordoma cancer stem cells (CCSCs) were identified using flow cytometry, sphere formation, and western blot analysis. …”
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CD4 T cell depletion increases memory differentiation of endogenous and CAR T cells and enhances the efficacy of Super2 and IL-33-armored CAR T cells against solid tumors by Chrystal Paulos, Mary Jo Turk, Megen C Wittling, Yina H Huang, Asmaa O Mohamed, David Tyler Boone, Shannon L Ferry, Melanie C Peck, Alicia M Santos, Haille E Soderholm

“…Background Responsiveness to chimeric antigen receptor (CAR) T cell therapy correlates with CAR T cell expansion and persistence in vivo. …”
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Unveiling causal immune cell–gene associations in multiple myeloma: insights from systematic reviews and Mendelian randomization analyses by Hui Zhang, Hui Zhang, Ling Zhang, Jing-Xuan Lian, Zhi-Fu Kou, Yu Zhu, Yu Zhu, Li-Tian Ma, Li-Tian Ma, Jin Zheng, Jin Zheng, Can-Jun Zhao, Can-Jun Zhao

“…BackgroundThe efficacy of novel chimeric antigen receptor T-cell (CAR-T) therapy is inconsistent, likely due to an incomplete understanding of the tumor microenvironment (TME). …”
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LLT1 overexpression renders allogeneic-NK resistance and facilitates the generation of enhanced universal CAR-T cells by Shuxian Zhu, Shiyu Zuo, Chuo Li, Xingjie You, Erlie Jiang, Xiaoming Feng, Yuechen Luo

“…We performed cytotoxicity, proliferation, and cytokine assays to evaluate the functionality of universal chimeric antigen receptor-T cell (UCAR-T) cells and conducted in vitro and in vivo assays, including allogeneic responses and RNA sequencing, to assess their resistance to allogeneic T and NK cells, anti-leukemia efficacy, and persistence in treating hematologic malignancies. …”
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Shed antigen-induced blocking effect on CAR-T cells targeting Glypican-3 in Hepatocellular Carcinoma by Wei Gao, Tong Ding, Beicheng Sun, Nan Li, Fang Gao, Meng Jia, Mitchell Ho, Na Li, Luan Sun, Zhanhui Gao, Lei Ao, Sujuan Ma, Peihua Lu, Shaochang Jia

“…Background Glypican-3 (GPC3), a cell surface glycoprotein that is pathologically highly expressed in hepatocellular carcinoma (HCC), is an attractive target for immunotherapies, including chimeric antigen receptor (CAR) T cells. The serum GPC3 is frequently elevated in HCC patients due to the shedding effect of cell surface GPC3. …”
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The molecular receptor NKBB enhances the persistence and anti-hepatocellular carcinoma activity of GPC3 CAR-T cells by Minghao Sui, Tiantian Liu, Xuanli Song, Ji Li, Han Ding, Yuqian Liu, Xinyu Wang, Huimin Liu, Yuchan Xue, Jianni Qi, Miao Zhang, Songbo Zhao, Qiang Zhu

“…Chimeric antigen receptor (CAR) T cells have encouraging results in the treatment of hematological malignancies. …”
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Impact of prior CAR T-cell therapy on mosunetuzumab efficacy in patients with relapsed or refractory B-cell lymphomas by Elise A. Chong, Elicia Penuel, Ellen B. Napier, Rachel K. Lundberg, Lihua E. Budde, Mazyar Shadman, Matthew J. Matasar, Nancy L. Bartlett, Ian W. Flinn, Francesc Bosch, Keith Fay, Andre Goy, Anita Kumar, Loretta J. Nastoupil, Michael C. Wei, Mei Wu, Shen Yin, Joseph A. Fraietta, Emeline R. Chong, Stephen J. Schuster

“…Abstract: Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)–modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown. …”
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Large-scale manufacturing and characterization of CMV-CD19CAR T cells by Stephen J Forman, Xiuli Wang, Ryan Urak, Miriam Walter, Min Guan, Tianxu Han, Vibhuti Vyas, Sheng-Hsuan Chien, Brenna Gittins, Mary C Clark, Sally Mokhtari, Angelo Cardoso, Don J Diamond, John Zaia, Ryotaro Nakamura

“…Background Adoptive transfer of CD19-specific chimeric antigen receptor (CD19CAR) T cells can induce dramatic disease regression in patients with B cell malignancies. …”
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Engineered T cells secreting αB7-H3-αCD3 bispecific engagers for enhanced anti-tumor activity against B7-H3 positive multiple myeloma: a novel therapeutic approach by Punchita Rujirachaivej, Teerapong Siriboonpiputtana, Kornkan Choomee, Kamonlapat Supimon, Thanich Sangsuwannukul, Pucharee Songprakhon, Krissada Natungnuy, Piriya Luangwattananun, Pornpimon Yuti, Mutita Junking, Pa-thai Yenchitsomanus

“…Abstract Background Multiple myeloma (MM) is an incurable plasma cell malignancy with increasing global incidence. Chimeric antigen receptor (CAR) T-cell therapy targeting BCMA has shown efficacy in relapsed or refractory MM, but it faces resistance due to antigen loss and the tumor microenvironment. …”
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ROR1 CAR-T cells and ferroptosis inducers orchestrate tumor ferroptosis via PC-PUFA2 by Dan Li, Wenjie Zhang, Ruiheng Wang, Shufeng Xie, Yixin Wang, Wanxin Guo, Zixuan Huang, Chaoqun Lu, Liang Shan, Han Liu, Lifang Ma, Xumin Hou, Zhenshu Xu, Jiayi Wang

“…Emerging therapies, such as chimeric antigen receptor (CAR)-T cell therapy, have shown promise but face significant challenges in targeting solid tumors. …”
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Off-the-shelf CAR-NK cells targeting immunogenic cell death marker ERp57 execute robust antitumor activity and have a synergistic effect with ICD inducer oxaliplatin by Jichao Sun, Dinglan Wu, Liuhai Zheng, Huifang Wang, Jihao Zhou, Guangwei Shi, Jingbo Ma, Yuke Jiang, Zhiyu Dong, Jiexuan Li, Yuan-Qiao He, Chengchao Xu, Zhijie Li, Jigang Wang

“…Background Chimeric antigen receptor natural killer (CAR-NK) therapy holds great promise for treating hematologic tumors, but its efficacy in solid tumors is limited owing to the lack of suitable targets and poor infiltration of engineered NK cells. …”
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